The osmotic energy, a large-scale clean energy source, can be converted to electricity directly by ion-selective membranes. None of the previously reported membranes meets all the crucial demands of ultrahigh power density, excellent mechanical stability, and upscaled fabrication. Here, we demonstrate a large-scale, robust mushroom-shaped (with stem and cap) nanochannel array membrane with an ultrathin selective layer and ultrahigh pore density, generating the power density up to 22.4 W?m-2 at a 500-fold salinity gradient, which is the highest value among those of upscaled membranes. The stem parts are a negative-charged one-dimensional (1D) nanochannel array with a density of ~1011 cm-2, deriving from a block copolymer self-assembly; while the cap parts, as the selective layer, are formed by chemically grafted single-molecule-layer hyperbranched polyethyleneimine equivalent to tens of 1D nanochannels per stem. The membrane design strategy provides a promising approach for large-scale osmotic energy conversion.Aberrant activation of Wnt/β-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/β-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and β-catenin-mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing β-catenin signaling. Compiled functional genomic screens and network analysis revealed unique epigenetic regulators of β-catenin transcriptional output, including the histone lysine methyltransferase 2A oncoprotein (KMT2A/Mll1). Using an integrative epigenomic and transcriptional profiling approach, we show that KMT2A loss diminishes the binding of β-catenin to consensus DNA motifs and the transcription of β-catenin targets in CRC. These results suggest that KMT2A may be a promising target for CRCs and highlight the broader potential for exploiting epigenetic modulation as a therapeutic strategy for β-catenin-driven malignancies.Virus-infected cells and cancers share metabolic commonalities that stem from their insatiable need to replicate while evading the host immune system. These similarities include hijacking signaling mechanisms that induce metabolic rewiring in the host to up-regulate nucleotide metabolism and, in parallel, suppress the immune response. In both cancer and viral infections, the host immune cells and, specifically, lymphocytes augment nucleotide synthesis to support their own proliferation and effector functions. Consequently, established treatment modalities targeting nucleotide metabolism against cancers and virally infected cells may result in restricted immune response. Encouragingly, following the introduction of immunotherapy against cancers, multiple studies improved our understanding for improving antigen presentation to the immune system. We propose here that understanding the immune consequences of targeting nucleotide metabolism against cancers may be harnessed to optimize therapy against viral infections.Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein (IL1RAP) in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing. IL1RAP knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. https://www.selleckchem.com/products/qx77.html Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.We introduce a neutron-gamma emission tomography (NGET) technique for rapid detection, three-dimensional imaging, and characterization of special nuclear materials like weapons-grade plutonium and uranium. The technique is adapted from fundamental nuclear physics research and represents a previously unexplored approach to the detection and imaging of small quantities of these materials. The method is demonstrated on a radiation portal monitor prototype system based on fast organic scintillators, measuring the characteristic fast time and energy correlations between particles emitted in nuclear fission processes. The use of these correlations in real time in conjunction with modern machine learning techniques provides unprecedented imaging efficiency and high spatial resolution. This imaging modality addresses global security threats from terrorism and the proliferation of nuclear weapons. It also provides enhanced capabilities for addressing different nuclear accident scenarios and for environmental radiological surveying.Papers on COVID-19 are being published at a high rate and concern many different topics. Innovative tools are needed to aid researchers to find patterns in this vast amount of literature to identify subsets of interest in an automated fashion.
We present a new online software resource with a friendly user interface that allows users to query and interact with visual representations of relationships between publications.
We publicly released an application called PLATIPUS (Publication Literature Analysis and Text Interaction Platform for User Studies) that allows researchers to interact with literature supplied by COVIDScholar via a visual analytics platform. This tool contains standard filtering capabilities based on authors, journals, high-level categories, and various research-specific details via natural language processing and dozens of customizable visualizations that dynamically update from a researcher's query.
PLATIPUS is available online and currently links to over 100,000 publications and is still growing.